Medical implants including iridium oxide

ABSTRACT

A medical implant includes iridium oxide. The iridium oxide has a plurality of Ir—O σ bonds and a plurality of Ir═O π bonds. The iridium oxide has a ratio of the Ir—O σ bonds to the Ir═O π bonds that is greater than 1.3.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 USC §119(e) to U.S.Provisional Patent Application Ser. No. 61/119,646, filed on Dec. 3,2008, the entire contents of which are hereby incorporated by reference

TECHNICAL FIELD

This invention relates to medical implants including iridium oxide, andmore particularly to endoprostheses including iridium oxide.

BACKGROUND

A medical implant can replace, support, or act as a missing biologicalstructure. Some examples of medical implants can include orthopedicimplants; bioscaffolding; endoprostheses such as stents, covered stents,and stent-grafts; bone screws; and aneurism coils. Some medical implantsare designed to erode under physiological conditions.

Medical endoprostheses can, for example, be used in various passagewaysin a body, such as arteries, other blood vessels, and other body lumens.These passageways sometimes become occluded or weakened. For example,the passageways can be occluded by a tumor, restricted by plaque, orweakened by an aneurysm. When this occurs, the passageway can bereopened or reinforced, or even replaced, with a medical endoprosthesis.An endoprosthesis is typically a tubular member that is placed in alumen in the body. Examples of endoprostheses include stents, coveredstents, and stent-grafts.

Endoprostheses can be delivered inside the body by a catheter thatsupports the endoprosthesis in a compacted or reduced-size form as theendoprosthesis is transported to a desired site. Upon reaching the site,the endoprosthesis is expanded, For example, so that it can contact thewalls of the lumen.

The expansion mechanism can include forcing the endoprosthesis to expandradially. For example, the expansion mechanism can include the cathetercarrying a balloon, which carries a balloon-expandable endoprosthesis.The balloon can be inflated to deform and to fix the expandedendoprosthesis at a predetermined position in contact with the lumenwall. The balloon can then be deflated, and the catheter withdrawn.

In another delivery technique, the endoprosthesis is formed of anelastic material that can be reversibly compacted and expanded, e.g.,elastically or through a material phase transition. During introductioninto the body, the endoprosthesis is restrained in a compactedcondition. Upon reaching the desired implantation site, the restraint isremoved, for example, by retracting a restraining device such as anouter sheath, enabling the endoprosthesis to self-expand by its owninternal elastic restoring force.

SUMMARY

A medical implant is described that includes iridium oxide having aplurality of Ir—O σ bonds and a plurality of Ir═O π bonds, the ratio ofthe Ir—O σ bonds to the Ir═O π bonds being greater than 1.3. In someembodiments, the ratio of Ir—O σ bonds to Ir═O π bonds is greater than1.45. In some embodiments, the ratio is less than 3. For example, theratio can be between 1.6 and 2.1. The iridium oxide can have a pluralityof Ir atoms having a mean valance state of less than 3.4+.

The iridium oxide can have a morphology of defined grains with an aspectratio of about 5:1 or more.

The iridium oxide can exhibit a charge of at least 0.0060 Coul/cm2 in acyclic voltammetry potentiodynamic electrochemical measurement having asweep rate no more than 50 mV/s. In some embodiments, the iridium oxidecan have less than 15% atomic carbon.

The iridium oxide can define an outer surface of the medical implant. Insome embodiments, the medical implant includes a base metal and theiridium oxide coats the base metal. The base metal can be selected fromthe group of stainless steels, stainless steels enhanced with radiopaqueelements, nickel-titanium alloys, cobalt alloys, titanium and titaniumalloys, platinum and platinum alloys, niobium and niobium alloys,tantalum and tantalum alloys, and combinations thereof.

The medical implant can include an electrode, the electrode comprisingthe iridium oxide.

The medical implant is, in some embodiments, an endoprosthesis (e.g., astent).

In some aspects, medical implant is described that includes iridiumoxide having a plurality of Ir atoms having a mean valance state of lessthan 3.4+.

In some embodiments, the Ir atoms having a mean valance state of between3.20+ and 3.35+. In some embodiments, the iridium oxide has a pluralityof Ir—O σ bonds and a plurality of Ir═O π bonds, the iridium oxidehaving a ratio of the Ir—O σ bonds to the Ir═O π bonds that is between1.45 and 3.0. In some embodiments, the medical device includes a basemetal. The iridium oxide can coat the base metal and defining an outersurface of the medical implant. The base metal can be selected from thegroup of stainless steels, stainless steels enhanced with radiopaqueelements, nickel-titanium alloys, cobalt alloys, titanium and titaniumalloys, platinum and platinum alloys, niobium and niobium alloys,tantalum and tantalum alloys, and combinations thereof. The medicalimplant can be an electrode for pacing or neural stimulation. In otherembodiments, the medical implant is an endoprosthesis.

In some aspects, method for making a medical implant is described. Themethod includes placing a medical implant or precursor thereof in aphysical vapor deposition processing chamber and depositing iridiumoxide on the medical implant or precursor thereof using a power of atleast 750 watts and a total pressure of between 3 mTorr and 7 mTorr. Insome embodiments, the process can use an oxygen partial pressure ofbetween 91% and 100%,

The details of one or more embodiments are set forth in the accompanyingdrawings and the description below. Other features, objects, andadvantages will be apparent from the description and drawings, and fromthe claims.

DESCRIPTION OF DRAWINGS

FIGS. 1A-1C are longitudinal cross-sectional views illustrating deliveryof a stent in a collapsed state, expansion of the stent, and deploymentof the stent.

FIG. 2 is a perspective view of a stent.

FIGS. 3A and 3B are IROX surface morphologies produced by PVD processes.

FIGS. 3C and 3D are IROX surface morphologies produced by thermaldecomposition processes.

FIGS. 4A-4D are Cyclic Voltammetry Scans of three different IROXsurfaces.

FIG. 5A depicts an iridium 4f core level spectra of the three differentIROX surfaces.

FIG. 5B depicts an Oxygen 1s core level spectra of the three differentIROX surfaces.

FIGS. 6A-6C depict deconvoluted Oxygen 1s XPS Core level spectra of thethree different IROX surfaces.

FIGS. 7A-7C depict deconvoluted Carbon 1s core level spectra of thethree different IROX surfaces.

FIG. 8A depicts inverted cylindrical physical vapor depositionprocessing chamber.

FIG. 8B depicts a second type of physical vapor deposition processingchamber.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Referring to FIGS. 1A-1C, a stent 20 is placed over a balloon 12 carriednear a distal end of a catheter 14, and is directed through the lumen 16(FIG. 1A) until the portion carrying the balloon and stent reaches theregion of an occlusion 18. The stent 20 is then radially expanded byinflating the balloon 12 and compressed against the vessel wall with theresult that occlusion 18 is compressed, and the vessel wall surroundingit undergoes a radial expansion (FIG. 1B). The pressure is then releasedfrom the balloon and the catheter is withdrawn from the vessel (FIG.1C).

Referring to FIG. 2, stent 20 can have the form of a tubular memberdefined by a plurality of struts, which include a plurality of bands 22and a plurality of connectors 24 that extend between and connectadjacent bands. During use, bands 22 can be expanded from an initial,small diameter to a larger diameter to contact the outer diameter ofstent 20 against a wall of a vessel, thereby maintaining the patency ofthe vessel. Connectors 24 can provide the stent 20 with flexibility andconformability that allow the stent to adapt to the contours of thevessel.

Stent 20 can include a stent body formed of a base metal and include aniridium oxide (IROX) coating. For example, IROX coatings are depicted inFIGS. 3A-3D. In some embodiments, the IROX coating is on only one side,e.g. the abluminal side. In other embodiments, the IROX coating cancover all of the sides of the stent body. In some embodiments, the stentcan include a second coating, such as a drug-eluting coating. In someembodiments, the second coating can be on only one side, e.g., theabluminal side. In other embodiments, the IROX coating defines an outersurface of the stent and the stent does not include any additionalexterior coatings over the IROX coating.

IROX is an electrically conductive, valence-changing metal oxide thatcrystallizes in the rutile structure. The iridium in IROX can eitherhave a valence state of Ir³⁺ and/or Ir⁴⁺. IROX can reduce restenosisthrough the catalytic reduction of hydrogen peroxide and otherprecursors to smooth muscle cell proliferation. IROX can also encourageendothelial growth to enhance endothelialization of the stent. When astent is introduced into a biological environment (e.g., in vivo), oneof the initial responses of the human body to the implantation of astent, particularly into the blood vessels, is the activation ofleukocytes, white blood cells which are one of the constituent elementsof the circulating blood system. This activation causes a release ofreactive oxygen compound production. One of the species released in thisprocess is hydrogen peroxide, H₂O₂, which is released by neutrophilgranulocytes, which constitute one of the many types of leukocytes. Thepresence of H₂O₂ may increase proliferation of smooth muscle cells andcompromise endothelial cell function, stimulating the expression ofsurface binding proteins which enhance the attachment of moreinflammatory cells. IROX can catalytically reduce hydrogen peroxide.IROX is also discussed further in Alt, U.S. Pat. No. 5,980,566. IROX canalso facilitate the adhesion of coatings onto an implant. For example,the presence of an IROX coating on a base metal of a stent can preventthe delamination of overlaying polymer coating (e.g., a drug-elutingcoating).

The relative amounts of Ir³⁺ and Ir⁴⁺ can impact the catalyticefficiency of the IROX in reducing H₂O₂. The IROX can have a meanvalance state of less than 3.4+, meaning that at least 60% of theIridium atoms present in the IROX have a valance state of 3+. In someembodiments, the IROX can have a mean valance state of between 3.20+ and3.35+ (e.g., about 3.3+). In addition to other possible reactionmechanisms, IROX can decompose H₂O₂ using the following mechanism, wherethe H₂O₂ acts as an oxidant and takes electrons from the Ir³⁺ and toconvert the Ir³⁺ into Ir⁴⁺. This proposed reaction mechanism indicatesthat the presence of Ir³⁺ improves the catalytic efficiency of IROXhaving a lower mean valance state.H₂O₂+Ir³⁺→Ir⁴⁺+H₂O3H₂O₂+2IrO(OH)→2IrO₂+4H₂O

IROX includes a plurality of Ir—O σ bonds (single bonds) and a pluralityof Ir═O π bonds (double bonds). The ratio of Ir—O σ bonds to Ir═O πbonds (“σ:π ratio”) in IROX can impact the catalytic efficiency of theof the IROX in reducing H₂O₂. The IROX can have a σ:π ratio of greaterthan 1.3. In some embodiments, the σ:π ratio can be between 1.3 and 3.In some embodiments, the σ:π ratio can be greater than 1.45. Morespecifically, the σ:π ratio can be between 1.6 and 2.1.

Iridium oxide can form many different chemical structures, even for agiven valance state. For example, Ir³⁺ can form Ir(OH)₃, IrO(OH), andIr₂O₃. Both IrO(OH) and Ir₂O₃ have one Ir—O σ bonds and one Ir═O π bondper iridium atom, while Ir(OH)₃ has 3 Ir—O σ bonds per iridium atom.IROX having Ir⁴⁺ can form IrO₂ and IrO(OH)₂. IrO₂ has two Ir═O π bondsper Iridium atom and IrO(OH)₂ has two Ir—O σ bonds and one Ir═O π bondper iridium atom. Other more complex Iridium oxide chemical structuresare also possible. The different chemical structures also can havevarious oxygen to iridium ratios. Methods of determining the σ:π ratiofor IROX samples and the relative amounts of Ir³⁺ and Ir⁴⁺ are discussedbelow in the Examples section.

The IROX can have a surface morphology of defined grains with an aspectratio of about 5:1 or more. In some embodiments, the IROX coating canhave an S_(dr) of about 100 or greater. The IROX coating can have thetypes of morphologies described in application U.S. Ser. No. 11/752,772,filed May 23, 2007, which is hereby incorporated by reference. In someembodiments, the IROX coating can have a rice grain surface morphology,such as the morphologies similar to those shown in FIGS. 3A and 3B. Inother embodiments, the IROX coating can have a mud-cracked SEMmorphology similar to the structures shown in FIGS. 3C and 3D.

The IROX coating can have capacitance of at least 0.006 Coul/cm² whenscanned in a cyclic voltammetry test at a rate of no more than 50 mV/s.The scan can be between −1.05 V to 1.2 V, between −0.6V and 1 V orbetween −0.3 V to 1 V. The cyclic voltammetry test can be preformed in aphosphate buffered saline solution at room temperature. In someembodiments, the IROX coating can have a capacitance of at least 0.008Coul/cm² when scanned in a Cyclic Voltammetry test at a rate of no morethan 50 mV/s. Examples of Cyclic Voltammetry evaluations of differentIROX samples are presented in the Examples section.

The IROX coating can be deposited by thermal decomposition, reactivelaser ablation, physical vapor deposition (PVD) or electrochemicaldeposition, which can each include a host of process parameters that canimpact the properties of the deposited IROX. Different depositionprocesses can result in different surface characteristics, differentamounts of carbonyl oxygen groups (C═O bonds), and different possibleσ:π ratios. For instance, thermal decomposition can have between 30percent and 50 percent atomic carbon while PVD can have between 10percent and 25 percent atomic carbon. The atomic carbon can formcarbonyl oxygen groups within the IROX. Furthermore, different processescan produce different morphologies. For example, physical vapordeposition (PVD) can be used to produce the rice grain morphologies ofFIGS. 3A and 3B, while thermal decomposition can be used to produce thecracked mud cake structures shown in FIGS. 3C and 3D. These processescan also be used to form other morphologies.

The operating parameters of the deposition system are selected to tunethe σ:π ratio of the IROX and the mean valance state of the iridiumatoms in the IROX, as well as other properties such as surfacemorphology. In particular, the power, total pressure, oxygen/argon ratioand sputter time can be adjusted to alter the σ:π ratio, the meanvalance state, and other properties. In some embodiments, physical vapordeposition processes use oxygen gas and argon gas where the oxygen gasmakes up greater than 90 percent of the gas in the PVD chamber. Theoxygen partial pressure can be in the range of between 91% to 100%(e.g., 92%). In some embodiments, the power is at least 750 watts (e.g.between 850 watts and 1000 watts) and the total pressure is between 3mTorr and 7 mTorr (e.g., between 4 mTorr and 6 mTorr). The depositiontime controls the thickness of the IROX and the stacking ofmorphological features. In embodiments, the deposition time is between 5minutes and 15 minutes (e.g. between 8 and 12 minutes). The overallthickness of the IROX can be between 50 nm and 500 nm (e.g. between 100nm and 300 nm). Specific PVD processing conditions are discussed in theExamples section.

Thermal decomposition can also be used to produce the IROX coating. Forexample, thermal decomposition can produce a mud-cracked morphologycoating shown in FIGS. 3C and 3D as seen using a scanning electronmicroscope. As discussed above, thermal decomposition can result in ahigher percentage of atomic carbon than PVD processes, which can resultin a higher percentage of carbonyl oxygen. In some embodiments, IROX isdeposited using thermal decomposition temperature of between 200 and 250degrees Celsius for less than about 10 minutes (e.g., between 1 minuteand 5 minutes). The IROX can be annealed afterwards for less than onehour (e.g., between 10 minutes and 50 minutes). Thermal decompositioncan also include steps of sand blasting and the application of aprecursor solution prior to heating the iridium containing precursormaterial to form the iridium oxide. For example, U.S. Patent ApplicationPublication Nos. 2006/0035026 and 2005/0131509 describe IROX depositionprocesses using thermal decomposition, which can be modified asdiscussed above, and are hereby incorporated by reference.

The stent can include (e.g., be manufactured from) a base metal, such asstainless steel (e.g., 316L, BioDur® 108 (UNS S29108)), and 304Lstainless steel, and an alloy including stainless steel and 5-60% byweight of one or more radiopaque elements (e.g., Pt, Ir, Au, W) (PERSS®)as described in US-2003-0018380-A1, US-2002-0144757-A1, andUS-2003-0077200-A1), Nitinol (a nickel-titanium alloy), cobalt alloyssuch as Elgiloy, L605 alloys, MP35N, titanium, titanium alloys (e.g.,Ti-6Al-4V, Ti-50Ta, Ti-10Ir), platinum, platinum alloys, niobium,niobium alloys (e.g., Nb-1Zr) Co-28Cr-6Mo, tantalum, and tantalumalloys. Other examples of materials are described in commonly assignedU.S. application Ser. No. 10/672,891, filed Sep. 26, 2003; and U.S.application Ser. No. 11/035,316, filed Jan. 3, 2005, which are bothhereby incorporated by reference. Other materials include elasticbiocompatible metal such as a superelastic or pseudo-elastic metalalloy, as described, For example, in Schetsky, L. McDonald, “ShapeMemory Alloys”, Encyclopedia of Chemical Technology (3rd ed.), JohnWiley & Sons, 1982, vol. 20. pp. 726-736; and commonly assigned U.S.application Ser. No. 10/346,487, filed Jan. 17, 2003. Any stentdescribed herein can be dyed or rendered radiopaque by addition of,e.g., radiopaque materials such as barium sulfate, platinum or gold, orby coating with a radiopaque material. For example, in some embodiments,the second coating 36 can be a radiopaque material.

The stent can be of a desired shape and size (e.g., coronary stents,aortic stents, peripheral vascular stents, gastrointestinal stents,urology stents, tracheal/bronchial stents, and neurology stents).Depending on the application, the stent can have a diameter of between,e.g., about 1 mm to about 46 mm. In certain embodiments, a coronarystent can have an expanded diameter of from about 2 mm to about 6 mm. Insome embodiments, a peripheral stent can have an expanded diameter offrom about 4 mm to about 24 mm. In certain embodiments, agastrointestinal and/or urology stent can have an expanded diameter offrom about 6 mm to about 30 mm. In some embodiments, a neurology stentcan have an expanded diameter of from about 1 mm to about 12 mm. AnAbdominal Aortic Aneurysm (AAA) stent and a Thoracic Aortic Aneurysm(TAA) stent can have a diameter from about 20 mm to about 46 mm. Thestent can be balloon-expandable, self-expandable, or a combination ofboth (e.g., U.S. Pat. No. 6,290,721). The ceramics can be used withother endoprostheses or medical implants, such as catheters, guidewires, and filters.

The stent 20 can, in some embodiments, include a second coating over theIROX. The second coating can be a polymer. In some embodiments, thesecond coating can be a drug eluting coating. Suitable drug elutingpolymers may be hydrophilic or hydrophobic. Suitable polymers include,for example, polycarboxylic acids, cellulosic polymers, includingcellulose acetate and cellulose nitrate, gelatin, polyvinylpyrrolidone,cross-linked polyvinylpyrrolidone, polyanhydrides including maleicanhydride polymers, polyamides, polyvinyl alcohols, copolymers of vinylmonomers such as EVA, polyvinyl ethers, polyvinyl aromatics such aspolystyrene and copolymers thereof with other vinyl monomers such asisobutylene, isoprene and butadiene, for example,styrene-isobutylene-styrene (SIBS), styrene-isoprene-styrene (SIS)copolymers, styrene-butadiene-styrene (SBS) copolymers, polyethyleneoxides, glycosaminoglycans, polysaccharides, polyesters includingpolyethylene terephthalate, polyacrylamides, polyethers, polyethersulfone, polycarbonate, polyalkylenes including polypropylene,polyethylene and high molecular weight polyethylene, halogeneratedpolyalkylenes including polytetrafluoroethylene, natural and syntheticrubbers including polyisoprene, polybutadiene, polyisobutylene andcopolymers thereof with other vinyl monomers such as styrene,polyurethanes, polyorthoesters, proteins, polypeptides, silicones,siloxane polymers, polylactic acid, polyglycolic acid, polycaprolactone,polyhydroxybutyrate valerate and blends and copolymers thereof as wellas other biodegradable, bioabsorbable and biostable polymers andcopolymers. Coatings from polymer dispersions such as polyurethanedispersions (BAYHDROL®, etc.) and acrylic latex dispersions are alsowithin the scope of the present invention. The polymer may be a proteinpolymer, fibrin, collagen and derivatives thereof, polysaccharides suchas celluloses, starches, dextrans, alginates and derivatives of thesepolysaccharides, an extracellular matrix component, hyaluronic acid, oranother biologic agent or a suitable mixture of any of these, forexample. In one embodiment, the preferred polymer is polyacrylic acid,available as HYDROPLUS® (Boston Scientific Corporation, Natick, Mass.),and described in U.S. Pat. No. 5,091,205, the disclosure of which ishereby incorporated herein by reference. U.S. Pat. No. 5,091,205describes medical implants coated with one or more polyisocyanates suchthat the devices become instantly lubricious when exposed to bodyfluids. In another preferred embodiment of the invention, the polymer isa copolymer of polylactic acid and polycaprolactone. Suitable polymersare discussed in U.S. Publication No. 2006/0038027. In embodiments, thepolymer is capable of absorbing a substantial amount of drug solution.When applied as a coating on a medical implant in accordance with thepresent invention, the dry polymer is typically on the order of fromabout 1 to about 50 microns thick. Very thin polymer coatings, e.g., ofabout 0.2-0.3 microns and much thicker coatings, e.g., more than 10microns, are also possible. Multiple layers of polymer coating can beprovided. Such multiple layers are of the same or different polymermaterials.

The terms “therapeutic agent”, “pharmaceutically active agent”,“pharmaceutically active material”, “pharmaceutically activeingredient”, “drug” and other related terms may be used interchangeablyherein and include, but are not limited to, small organic molecules,peptides, oligopeptides, proteins, nucleic acids, oligonucleotides,genetic therapeutic agents, non-genetic therapeutic agents, vectors fordelivery of genetic therapeutic agents, cells, and therapeutic agentsidentified as candidates for vascular treatment regimens, For example,as agents that reduce or inhibit restenosis. By small organic moleculeit is meant an organic molecule having 50 or fewer carbon atoms, andfewer than 100 non-hydrogen atoms in total.

Exemplary therapeutic agents include, e.g., anti-thrombogenic agents(e.g., heparin); anti-proliferative/anti-mitotic agents (e.g.,paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine,inhibitors of smooth muscle cell proliferation (e.g., monoclonalantibodies), and thymidine kinase inhibitors); antioxidants;anti-inflammatory agents (e.g., dexamethasone, prednisolone,corticosterone); anesthetic agents (e.g., lidocaine, bupivacaine andropivacaine); anti-coagulants; antibiotics (e.g., erythromycin,triclosan, cephalosporins, and aminoglycosides); agents that stimulateendothelial cell growth and/or attachment. Therapeutic agents can benonionic, or they can be anionic and/or cationic in nature. Therapeuticagents can be used singularly, or in combination. Preferred therapeuticagents include inhibitors of restenosis (e.g., paclitaxel),anti-proliferative agents (e.g., cisplatin), and antibiotics (e.g.,erythromycin). Additional examples of therapeutic agents are describedin U.S. Published Patent Application No. 2005/0216074. Polymers for drugelution coatings are also disclosed in U.S. Published Patent ApplicationNo. 2005/019265A. A functional molecule, e.g. an organic, drug, polymer,protein, DNA, and similar material can be incorporated into groves,pits, void spaces, and other features of the ceramic.

The stents described herein can be configured for vascular, e.g.coronary and peripheral vasculature or non-vascular lumens. For example,they can be configured for use in the esophagus or the prostate. Otherlumens include biliary lumens, hepatic lumens, pancreatic lumens,uretheral lumens and ureteral lumens.

IROX can also be used in other medical implants. IROX can improve thebiocompatibility of a medical implant. Medical implants other thanstents include orthopedic implants; bioscaffolding; bone screws;aneurism coils; heart and brain pacemakers, neural stimulators, andother endoprostheses such as covered stents and stent-grafts. IROXhaving a σ:π ratio greater than 1.3 and/or a mean valance state of theiridium in the IROX of less than 3.4+ can improve the catalyticefficiency of the IROX. The IROX can be useful in heart and brainpacemakers and as neural stimulators as a coating for electrodes becausea surface capacitance of greater than 0.006 Coul/cm² can reducepolarization losses of the voltage waveform for a constant current pulseused to stimulate the heart or brain. This can result in improved chargeinjection properties for the electrode. This can also reducepolarization loses at the electrode's surface.

EXAMPLES

Three IROX layers on stents were deposited in PVD processes using thefollowing process conditions shown in Table I.

TABLE I Process I Process II Process III Oxygen Gas to 40% 33% 92% ArgonGas Ratio Total Pressure 10 mTorr 10 mTorr 4.7 mTorr Magnetron Power 300Watts 100 Watts 890 Watts (½ cathode) (Current controlled: 1.5 Amps)Deposition Time 3 minutes 3.75 minutes 10 minutes PVD apparatusCylindrical Cylindrical Planer Magnetron Magnetron Magnetron

FIG. 8A depicts a cylindrical magnetron. The cylindrical magnetron has acylindrical iridium target and includes a 20 centimeter diameterchamber. The cylindrical magnetron can be an inverted cylindricalphysical vapor deposition as described in Siegfried et al., Society ofVacuum Coaters, 39^(th) Annual Technical Conference Proceedings (1996),p. 97; Glocker et al., Society of Vacuum Coaters, 43^(rd) AnnualTechnical Conference Proceedings-Denver, Apr. 15-20, 2000, p. 81; andSVC: Society of Vacuum Coatings: C-103, An Introduction to PhysicalVapor Deposition (PVD) Processes and C-248—Sputter Deposition inManufacturing, available from SVC 71 Pinion Hill, Nebr., Albuquerque, N.Mex. 87122-6726. A suitable cathode system is the Model 514, availablefrom Isoflux, Inc., Rochester, N.Y. FIG. 8B depicts a planar magnetronhaving a planar target and includes a 45 centimeter diameter chamber.The planar magnetron can have pulsed bias capabilities. Other sputteringtechniques include closed loop cathode magnetron sputtering. Pulsedlaser deposition is described in application U.S. Ser. No. 11/752,735,filed May 23, 2007. Formation of IROX is also described in Cho et al.,Jpn. J. Appl. Phys. 36(I)3B: 1722-1727 (1997), and Wessling et al., J.Micromech. Microeng. 16:5142-5148 (2006).

A comparison of IROX samples produced by PVD processes I, II, and IIIshowed that the IROX samples show similar surface morphologies duringvisual inspection. At micro-level the IROX coatings produced by PVD aresmooth, dense and featureless. At nano-level, however, the grainstructural features of the coating are clearly evident. FIG. 3 A depictsthe surface morphology of IROX samples produced using Process I and FIG.3B depicts the surface morphology of IROX samples produced using ProcessIII. All three processes produce rice grain surface morphologies. Thesurface morphology of IROX coatings were examined by Zeiss Supra 35VPField Emission Scanning Electron Microscope (FESEM).

An electrochemical evaluation of samples produced by the three differentprocesses, however, showed that IROX samples produced by process IIIhave a larger capacitance than IROX samples produced by processes I andII, indicating that process III creates a larger surface area thanprocesses I and II. In a series of tests, IROX samples produced by eachof processes I, II, and III were scanned in different Cyclic Voltammetryexperiments. The cyclic voltammetry tests were conducted in phosphatebuffered saline solution at room temperature and ambient conditions,using stents coated with the IROX sample films as working electrodes,platinum wires as counter/auxiliary electrodes, and a saturated Ag/AgClwire as a reference electrode. Solartron 1470E Multi-channelPotentiostat/Galvanostat coupled with 1455 Frequency Response Analyzer(FRA) and MultiStat/CorrWare/ZPlot software was used for dataacquisition and analysis. Cyclic voltammograms were recorded usingpotential scan rates between 5 and 350 mV/s with potential windowsranging from −1.05 to 1.2 V and from −0.3 V to 1 V for the slower scans.The electrochemical impedance data were recorded using a 10 mV amplitudeof sinusoidal voltage around the open circuit potential (OCP) over afrequency range from 100 KHz to 0.1 Hz. The capacitance values ofiridium oxide sample films were derived by integration of cyclicvoltammograms and by fitting the EIS data with the appropriateequivalent circuits.

FIG. 4A depicts the results of a cyclic voltammetry test of the samplesscanned at a rate of 50 mV/s between −0.6 V to 1 V. The test of FIG. 4Ashowed an average capacitance of the IROX samples produced by process Iof 0.0038844 Coul/cm², an average capacitance of the IROX samplesproduced by process II of 0.0048358 Coul/cm², and an average capacitancethe IROX samples produced by process III of 0.0086621 Coul/cm². FIG. 4Bdepicts the results of a cyclic voltammetry test of the samples scannedat a rate of 50 mV/s between −0.5 V to 0.9 V. The test of FIG. 4B showedan average capacitance of the IROX samples produced by process I of0.0036572 Coul/cm², an average capacitance of the IROX samples producedby process II of 0.004394 Coul/cm², and an average capacitance of theIROX samples produced by process III of 0.0082963 Coul/cm². Thecapacitance did not show dependence on the scan rate for the scans atrates of between 5 to 50 mV/s. FIGS. 4C and 4D depict the results ofcyclic voltammetry tests of the samples at scan rates of 200 mV/s and350 mV/s respectfully. FIGS. 4C and 4D also showed a larger chargecapacity for IROX samples produced by process III. Scans faster than 50mV/s, however, showed smaller capacitance values, which could be due tothe faster scan rates resulting in less probing of deeper layers.

An Auger Electron Spectroscopy (AES) analysis of the IROX samples wasalso preformed. A PHI Model 680 Field Emission Nanoprobe was used fordata acquisition and analysis. Auger electrons were excited with aprimary electron beam voltage of 10 keV, an absorbed beam current of 8nA at 55° sample tilt. Common carbon contamination, evident from the C(KLL) signal at 272 eV were at low levels of ˜15% at. The detectednitrogen impurity were at trace levels. The appearance of intense AugerO KL_(2,3)L_(2,3) signal at 512 eV in Iridium Auger signals, indicatesthe presence of oxidized iridium. The Auger spectra for each sample,however, indicated an O to Ir ratio of ˜1, which suggests that theoxides are reduced due to the electron beam damage due to the AESprocess. Accordingly, AES spectra can only provide a qualitativeestimate of the elemental atomic composition of IROX.

The composition of IROX, however, can be determined by x-rayphotoelectron spectroscopy (XPS). After argon sputtering, chemicalstates and elemental composition analysis by X-ray photoelectronspectroscopy of each IROX surface was conducted using PHI Quanterascanning XPS, equipped with a monochromatic Al Kα (1486.6 eV) X-raysource, at a base pressure bellow 10⁻⁹ mbar. The binding energy (BE)scale was calibrated relative to the BE of C 1s. The analyzed areas forsurvey and high resolution spectra were 300 and 150 μm respectively.Survey spectra were acquired at a detection angle of 45°. Highresolution core level spectra were collected at pass energy of 55 eV.Least-square curve-fitting of the Ir 4f, O 1s and C 1s spectra wasperformed based on the summed 90%/10% Gaussian-Lorentzian functions witha Shirley background subtraction. The atomic surface composition of IROXcoatings was calculated from the area of core level photoelectron peakscorrected by sensitivity factors of the respective elements from the PHIMultiPak software package. The relative concentration of the functionalgroups was determined from the areas under the corresponding resolvedcomponents with respect to the total core level photoemission. Elementalsurface composition was also confirmed by the Auger ElectronSpectroscopy (AES).

FIG. 5A shows the Iridium 4f core level spectra for samples of IROXproduced by each process. The Iridium 4f core level spectra does notallow for a significant distinction between the IROX samples from eachprocess, even when deconvoluted. FIG. 5B, however, shows the Oxygen 1score level spectra for samples of IROX produced by each of processes I,II, and III. As shown, each process produces a different Oxygen 1s corelevel spectra shapes. When deconvoluted, as shown in FIGS. 6A-6C, therelative amounts of oxygen σ (single) bonds can be determined by thesize of the peak 62 and the relative amounts of oxygen π (double) bondscan be determined by the size of peak 64. FIG. 6A depicts thedeconvoluted Oxygen 1s core level spectra for IROX produced by processI. FIG. 6B depicts the deconvoluted Oxygen 1s core level spectra forIROX produced by process II. FIG. 6C depicts the deconvoluted Oxygen 1score level spectra for IROX produced by process III. As shown, IROXproduced by process III has a smaller oxygen π bond peak 64.

The Oxygen 1s core level spectra, however, does not always allow for thecalculation of the σ:π ratio due to the presence of carbonyl oxygen inthe IROX. As discussed above, many of the IROX deposition processes canincorporate between 10 and 50 percent atomic carbon and producenon-trace amounts of carbonyl oxygen. It is possible, however, to useCarbon is XPS core level spectra data to determine amount ofoxygen-carbon bonds present due to the presence of carbonyl oxygen.FIGS. 7A-7C depict the deconvoluted Carbon 1s core level data for IROXsamples produced by process I-III respectively. Peak 72 of thedeconvoluted data represents the relative amount of carbon-oxygen πbonds. The amount of carbon-oxygen π bonds can then be subtracted fromthe 1s XPS σ oxygen bond value to determine the relative number of Ir—Oσ bonds to the number of Ir═O π bonds.

TABLE 2 O functional group % at O in O in Ir—O σ C O Ir C functionalgroup % at Ir═O π bonds + O in O in Ir—O σ Sample % at % at % at C—C C—OC═O bonds C═O bonds C—O Process I 11.3 63.0 25.7 6.8 2.9 1.6 35.3 20.218.6 7.6 20.6-1.6 Process I 10.4 62.8 26.8 6.3 2.6 1.46 35.2 20.1 18.67.5  20.1-1.46 Process I 13.0 60.8 26.3 8.97 2.7 1.3 35.9 18.8 17.5 6.118.8-1.3 Process I mean 11.6 1.45 19.7 18.2 Process II 14.2 61.2 24.69.4 3.5 1.3 33.05 20.8 19.5 7.3 Process II 14.2 61.0 24.7 8.1 4.4 1.732.3 20.7 19 7.9 Process II 17.6 58.9 23.5 11.4 4.2 1.9 30.6 21.2 19.37.1 Process II mean 15.3 1.63 20.9 19.3 Process III 15.2 61.6 23.2 10.33.0 1.8 18.5 33.9 32.1 9.2 Process III 19.0 59.0 22.0 12.2 4.4 2.5 20.629.5 27 8.8 Process III 18.7 59.0 22.4 12.2 4.3 2.1 21.2 29.5 27.4 8.3Process III mean 17.6 2.1 30.97 28.83

TABLE 3 O in Ir═O O in Ir—O C O Ir O in C—O O in IROX Σ O in π bonds σbonds Sample % at % at % at % at % at IROX/Ir % at % atO_(IrOx)/O_(IrOz) Process I 11.3 63.0 25.7 4.5 58.5 2.276 35.3 18.61.898 Process I 10.4 62.8 26.8 4.1 58.7 2.19 35.2 18.6 1.892 Process I13.0 60.8 26.3 4 56.8 2.16 35.9 17.5 2.05 Process I mean 26.3 2.21 35.4718.23 1.95 Process II 14.2 61.2 24.6 4.8 56.4 2.293 33.05 19.5 1.695Process II 14.2 61.0 24.7 6.1 54.9 2.223 32.3 19 1.7 Process II 17.658.9 23.5 6.1 52.8 2.247 30.6 19.3 1.585 Process II mean 24.3 2.25 32.019.3 1.66 Process III 15.2 61.6 23.2 4.8 56.8 2.448 18.5 32.1 0.576Process III 19.0 59.0 22.0 6.9 52.1 2.368 20.6 27 0.763 Process III 18.759.0 22.4 6.4 52.6 2.348 21.2 27.4 0.774 Process III mean 22.5 2.39 20.128.83 0.704

The average chemical structure of IROX is determined using the formulaof IrO_(x)(OH)_(y), where x and y are calculated from the data in Tables2 and 3. The σ:π ratio is equal to y divided by x. The mean valancestate of the IROX is 2x+y. The value of x is calculated to be the atomicpercent of oxygen in Ir═O π bonds divided by the atomic percent ofiridium. As discussed above, the amount of oxygen in Ir═O π bonds isdetermined by a deconvolution of the Oxygen 1s core level spectra data.The amount of iridium is calculated by XPS data. The value of y iscalculated by calculating the ratio of oxygen in IROX to iridium andsubtracting the value of x. The amount of oxygen in IROX is calculatedby from detecting the amount of total oxygen from the Oxygen 1s corelevel spectra data and subtracting the amount of oxygen due to thepresence of carbon-oxygen bonds from the Carbon 1s XPS core levelspectra data. The y value is calculated by subtracting the x value fromthe ratio to the oxygen in IROX to iridium due to possible errors in thedeconvolution of the XPS data for determining the amount of oxygen inIr—O σ bonds.

For example, process I is determined to have an average chemicalstructure of IrO_(1.35)(OH)_(0.86), a σ:π ratio of about 0.64, and amean iridium valance state of about 3.56. The value of x for process Iis determined by dividing the atomic percent of oxygen in Ir═O π bonds,which is 35.47, by the atomic percentage of iridium, which is 26.3, toyield an x value of about 1.35. The value for y for process I isdetermined by dividing the sum of oxygen in IROX, which is an average of58, divided by the atomic percentage of iridium, which is 26.3, to yielda value of 2.21 and subtracting the value of x, which is 1.35, to yielda y value of 0.86. The σ:π ratio of about 0.64 is calculated by dividingthe y value by the x value and the mean iridium valance state iscalculated by multiplying the x value by two and adding the y value.Process II is determined to have an average chemical structure ofIrO_(1.32)(OH)_(0.93), a σ:π ratio of about 0.70, and a mean iridiumvalance state of about 3.57. Process III is determined to have anaverage chemical structure of IrO_(0.89)(OH)_(1.5), a σ:π ratio of about1.69, and a mean iridium valance state of about 3.28. The differentsamples of IROX produced by process III shown in Tables 2 and 3 have thefollowing formulas, σ:π ratios, and mean valance states: IrO_(0.80)(OH)_(1.65), about 2.06, and about 3.25; IrO_(0.94)(OH)_(1.43), about1.52, and about 3.31; and IrO_(0.95)(OH)_(1.40), about 1.47, and about3.30.

A number of embodiments have been described. Nevertheless, it will beunderstood that various modifications may be made without departing fromthe spirit and scope of this disclosure. Accordingly, other embodimentsare within the scope of the following claims.

1. A medical implant comprising iridium oxide, the iridium oxide havinga plurality of Ir—O σ bonds and a plurality of Ir═O π bonds, the iridiumoxide having a ratio of the Ir—O σ bonds to the Ir═O π bonds that isbetween 1.6 and 2.1.
 2. The medical implant of claim 1, wherein theiridium oxide has a plurality of Ir atoms having a mean valance state ofless than 3.4+.
 3. The medical implant of claim 1, wherein the iridiumoxide comprises a morphology of defined grains with an aspect ratio ofabout 5:1 or more.
 4. The medical implant of claim 1, wherein theiridium oxide exhibits a charge of at least 0.0060 Coul/cm² in a cyclicvoltammetry potentiodynamic electrochemical measurement having a sweeprate no more than 50 mV/s.
 5. The medical implant of claim 1, whereinthe iridium oxide defines an outer surface of the medical implant. 6.The medical implant of claim 1, further comprising a base metal, theiridium oxide coating the base metal.
 7. The medical implant of claim 6,wherein the base metal is selected from the group consisting ofstainless steels, stainless steels enhanced with radiopaque elements,nickel-titanium alloys, cobalt alloys, titanium and titanium alloys,platinum and platinum alloys, niobium and niobium alloys, tantalum andtantalum alloys, and combinations thereof.
 8. The medical implant ofclaim 1, wherein the medical implant comprises an electrode, theelectrode comprising the iridium oxide.
 9. The medical implant of claim1, wherein the medical implant is an endoprosthesis.
 10. The medicalimplant of claim 9, wherein the endoprosthesis is a stent.
 11. Themedical implant of claim 1, wherein the Ir atoms having a mean valancestate of between 3.20+ and 3.35+.
 12. The medical implant of claim 1,wherein the iridium oxide is deposited on to a medical implant orprecursor thereof in a physical vapor deposition processing chamberusing a power of at least 750 watts, and a total pressure of between 3mTorr and 7 mTorr.
 13. A medical implant comprising iridium oxide, theiridium oxide having a plurality of Ir atoms having a mean valance stateof between 3.20+ and 3.35+.
 14. The medical implant of claim 13, whereinthe iridium oxide has a plurality of Ir—O σ bonds and a plurality ofIr═O π bonds, the iridium oxide having a ratio of the Ir—O σ bonds tothe Ir═O π bonds that is between 1.45 and 3.0.
 15. The medical implantof claim 14, wherein the ratio is between 1.6 and 2.1.
 16. The medicalimplant of claim 13, further comprising a base metal, the iridium oxidecoating the base metal and defining an outer surface of the medicalimplant, the base metal being selected from the group consisting ofstainless steels, stainless steels enhanced with radiopaque elements,nickel-titanium alloys, cobalt alloys, titanium and titanium alloys,platinum and platinum alloys, niobium and niobium alloys, tantalum andtantalum alloys, and combinations thereof.
 17. The medical implant ofclaim 13, wherein the medical implant comprises an electrode, theelectrode comprising the iridium oxide.
 18. The medical implant of claim13, wherein the medical implant is an endoprosthesis.
 19. The medicalimplant of claim 13, wherein the iridium oxide is deposited on to amedical implant or precursor thereof in a physical vapor depositionprocessing chamber using a power of at least 750 watts, and a totalpressure of between 3 mTorr and 7 mTorr.
 20. An endoprosthesiscomprising: a tublular member defined by a plurality of bands and aplurality of connectors that extend between and connect adjacent bands,the tubular member comprising a base metal; and a coating on the tubularmember, the coating comprising iridium oxide, the iridium oxide having aplurality of Ir—O σ bonds and a plurality of Ir═O π bonds, the iridiumoxide having a ratio of the Ir—O σ bonds to the Ir═O π bonds that isbetween 1.6 and 2.1, the iridium oxide having a plurality of Ir atomshaving a mean valance state of between 3.20+ and 3.35+.